A Phase III, randomized, multicenter, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current integrase inhibitor, NNRTI, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed
- Conditions
- Human immunodeficiency virus type 1 (HIV-1)MedDRA version: 20.1 Level: LLT Classification code 10003582 Term: Asymptomatic human immunodeficiency virus type I infection System Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2014-005147-40-BE
- Lead Sponsor
- ViiV Healthcare UK Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 510
Eligible subjects must:
- be able to understand and c
omply with protocol requirements, instructions, and restrictions;
- be likely to complete the study as planned;
- be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g., no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country, etc.).
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. HIV-1 infected men or women =18 years of age;
2.Must be on uninterrupted current regimen (either the initial or second cART regimen) for at least 6 months prior to Screening.
Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns or
access to medications, or convenience/simplification.
Acceptable stable cART regimens prior to Screening include 2 NRTIs plus:
- INI (either the initial or second cART regimen)
- NNRTI (either the initial or second cART regimen)
- Boosted PI (or atazanavir [ATV] unboosted) (either the initial or second PI-based cART regimen)
3. Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening;
4. Plasma HIV-1 RNA <50 c/mL at Screening;
5. A female, may be eligible to enter and participate in the study if she:
a. is of non-child-bearing potential either defined as post-menopausal (12 months of spontaneous amenorrhea and =45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
b. is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
- Complete abstinence from intercourse from 2 weeks prior to administration of study drug, throughout the study, and for at least 2 weeks after discontinuation of all study medications and completion of the Follow-up visit;
- Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see the SPM for a listing describing criteria of approved IUDs);
- Male partner sterilization with documentation of azoospermia prior to the female subject’s entry into the study and this male is the sole partner for that subject; [Hatcher, 2011]. The documentation on male sterility can come from the site personnel’s review of subject’s medical records, medical examination, and/or semen analysis, or medical history interview provided by her or her partner.
- Approved hormonal contraception for subjects randomly assigned to
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Exclusionary Criteria prior to Screening or Day 1
1. Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement >=50 c/mL;
2. Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL;
3. Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, 2 or more plasma HIV-1 RNA measurements >=50 c/mL;
4. Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns;
5. Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV-1 RNA measurement > or = 400 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen);
Exclusionary medical conditions
6. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study;
7. Any evidence of an active Centers for Disease Control and Prevention (CDC) Category C disease. Exceptions include cutaneous Kaposi’s sarcoma not requiring systemic therapy and historic CD4+ lymphocyte counts of <200 cells/mm3;
8. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh Classification (Appendix 2 of study Protocol, p97);
9. Unstable liver disease (as defined by the presence of any of the following: ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);
10. Evidence of Hepatitis B virus (HBV) infection based on the results of testing at screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), and Hepatitis B surface antibody (HBsAb) as follows:
- Subjects positive for HBsAg are excluded;
- Subjects positive for anti-HBc (negative HBsAg status) and negative for HBsAb are excluded.
NOTE: Subjects positive for anti-HBc (negative HBsAg status) and positive for HBsAb are immune to HBV and are not exluded.
11. Subjects with an anticipated need for any Hepatitis C virus (HCV) therapy during the Early Switch Phase and for interferon-based therapy for HCV throughout the entire study period;
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
12. History or presence of allergy to the study drugs or their components or drugs of their class;
13. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carci
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method